Cancer is one of the main causes of death in the world. Although significant efforts have been made to find new approaches for treating cancer, the primary treatment options remain surgery, chemotherapy and radiation therapy, either alone or in combination. Surgery and radiation therapy, however, are generally useful only for defined types of cancer. Chemotherapy is the method that is generally useful in treating patients with metastatic cancer or diffuse cancers, such as leukemias. Although chemotherapy can provide a therapeutic benefit, it often fails to result in cure of the disease due to the patient's cancer cells becoming resistant to the chemotherapeutic agent. Due, in part, to the likelihood of cancer cells becoming resistant to a chemotherapeutic agent, such agents are commonly used in combination to treat patients.
Similarly, infectious diseases caused by microorganisms are becoming increasingly difficult to treat and cure. Particularly, more and more microorganisms are developing resistance to current antimicrobial agents.
Furthermore, a growing number of diseases are classified as inflammatory diseases. Such diseases include conditions such as asthma. These diseases continue to affect larger and larger numbers of people worldwide, despite new therapies and medical advances.
Proteasome inhibitors (PIs) are a proven class of therapeutic agents in the treatment of cancers including multiple myeloma (MM), Waldenstr öm macroglobulinemia, and mantle cell lymphoma. These proteasome inhibitors have also showed promise in treating autoimmune diseases in animal models. For example, studies in mice bearing human skin grafts found a reduction in the size of lesions from psoriasis after treatment with a proteasome inhibitor. These inhibitors also showed positive effects in rodent models of asthma. In addition proteasorne inhibitors have shown promising results in treating microbial infections.
Proteasome inhibitors (PIs) are chemically classified into boronates, beta-lactams, epoxyketones, and peptide amides. Boronic acid and ester compounds hold particular promise as inhibitors of the proteasome and display a variety of pharmaceutically useful biological activities.